myelin-oligodendrocyte-glycoprotein-(35-55) and nitroflurbiprofen

Nitric oxide (NO)-releasing non-steroidal anti-inflammatory drugs (NSAIDs) have been reported to have a safer profile and additional anti-inflammatory and immuno-modulatory properties compared to parent compounds. Preventive treatment of experimental autoimmune encephalomyelitis (EAE)-induced in C57BL/6 mice by immunization with myelin oligodendrocyte glycoprotein (MOG) peptide 35-55-with the NO-releasing derivative of flurbiprofen HCT1026 delayed disease onset and significantly decreased disease severity. HCT1026 treatment was associated to (i) decreased mRNA levels of pro-inflammatory cytokines, caspase-1, and iNOS in blood cells; (ii) decreased ability of encephalitogenic T cells to proliferate; (iii) reduced number of central nervous system (CNS)-infiltrating T cells; (iv) decreased axonal loss and demyelination; (v) increased CD4(+) CD69(-) CD25(+) regulatory T cells in the spleen.

Topics: Administration, Oral; Adoptive Transfer; Animals; Antigens, CD; Antigens, Differentiation, T-Lymphocyte; CD4-Positive T-Lymphocytes; Cell Movement; Central Nervous System; Cytokines; Encephalomyelitis, Autoimmune, Experimental; Epitopes, T-Lymphocyte; Female; Flurbiprofen; Glycoproteins; Growth Inhibitors; Immunosuppressive Agents; Interleukin-10; Lectins, C-Type; Lymphocyte Count; Mice; Mice, Inbred C57BL; Mice, Knockout; Myelin-Oligodendrocyte Glycoprotein; Nitric Oxide; Peptide Fragments; Receptors, Interleukin-2; RNA, Messenger; Spleen; T-Lymphocyte Subsets